Department of Chemistry , University of Texas at Austin , Austin , Texas 78712 , United States.
KAUST Catalysis Center and Division of Physical Sciences and Engineering , King Abdullah University of Science and Technology (KAUST) , Thuwal 23955-6900 , Saudi Arabia.
J Am Chem Soc. 2019 Feb 6;141(5):2087-2096. doi: 10.1021/jacs.8b11868. Epub 2019 Jan 25.
Iridium complexes modified by the chiral phosphine ligand PhanePhos catalyze the 2-propanol-mediated reductive coupling of diverse 1,1-disubstituted allenes 1a-1u with fluoral hydrate 2a to form CF-substituted secondary alcohols 3a-3u that incorporate acyclic quaternary carbon-containing stereodiads. By exploiting concentration-dependent stereoselectivity effects related to the interconversion of kinetic ( Z)- and thermodynamic ( E)-σ-allyliridium isomers, adducts 3a-3u are formed with complete levels of branched regioselectivity and high levels of anti-diastereo- and enantioselectivity. The utility of this method for construction of CF-oxetanes and CF-azetidines is illustrated by the formation of 4a and 6a, respectively. Studies of the reaction mechanism aimed at illuminating the singular effectiveness of PhanePhos as a supporting ligand in this and related transformations have led to the identification of a chromatographically stable cyclometalated iridium-( R)-PhanePhos complex, Ir-PP-I, that is catalytically competent for allene-fluoral reductive coupling and previously reported transfer hydrogenative C-C couplings of dienes or CF-allenes with methanol. Deuterium labeling studies, reaction progress kinetic analysis (RPKA) and computational studies corroborate a catalytic mechanism involving rapid allene hydrometalation followed by turnover-limiting carbonyl addition. A computationally determined stereochemical model shows that the ortho-CH group of the cyclometalated iridium-PhanePhos complex plays a key role in directing diastereo- and enantioselectivity. The collective data provide key insights into the structural-interactional features of allyliridium complexes required to enforce nucleophilic character, which should inform the design of related cyclometalated catalysts for umpoled allylation.
手性膦配体 PhanePhos 修饰的铱配合物催化各种 1,1-二取代烯丙基 1a-1u 与氟醛水合物 2a 在 2-丙醇介导下的还原偶联，形成含有非环季碳立体双稠合的 CF 取代的仲醇 3a-3u。通过利用与动力学（Z）和热力学（E）-σ-烯丙基铱异构体的互变相关的浓度依赖性立体选择性效应，立体选择性地以完全的支化区域选择性和高的反式-非对映选择性和对映选择性形成加合物 3a-3u。该方法在构建 CF-氧杂环丁烷和 CF-氮杂环丁烷中的应用分别通过形成 4a 和 6a 得到了说明。对反应机理的研究旨在阐明 PhanePhos 作为支持配体在这种和相关转化中独特有效性的研究，导致了一种色谱稳定的环金属化铱-(R)-PhanePhos 配合物 Ir-PP-I 的鉴定，该配合物对烯丙基-氟醛还原偶联以及先前报道的二烯或 CF-烯丙基与甲醇的转移氢化 C-C 偶联具有催化能力。氘标记研究、反应进度动力学分析（RPKA）和计算研究证实了一种涉及快速烯丙基氢金属化随后是周转限制的羰基加成的催化机制。计算确定的立体化学模型表明，环金属化铱-PhanePhos 配合物的邻-CH 基团在控制非对映选择性和对映选择性方面起着关键作用。这些数据提供了对需要强制亲核性的烯丙基铱配合物的结构-相互作用特征的关键见解，这应该为设计相关的未极化烯丙化的环金属化催化剂提供信息。
